Small and neutral Tc(v)O BAT, bisaminoethanethiol (N2S2) complexes for developing new brain imaging agents.
Bisaminoethanethiol (BAT) ligands with various gem-dimethyl and amide groups were prepared, and the corresponding neutral Tc-99m complexes were prepared and evaluated for their relative stabilities by ligand-exchange reactions. It was demonstrated that technetium complexes containing gem-dimethyl substituents have higher lipophilicities, whereas those with an amide group possess greater stability, which enhances ligand-exchange reaction. The most interesting observation was that the brain uptake in rats is not determined only by lipophilicity. Apparently, Tc-99m complexes with an amide functional group display lower brain uptakes in rats compared to those without an amide group. The brain uptake was strongly influenced by substituents on the BAT ligand. These factors are critically important and should be taken into consideration when designing Tc-99m-labeled agents for CNS receptor imaging.
Oya
S
S
Department of Radiology, University of Pennsylvania, Philadelphia 19104, USA.
Plössl
K
K
Kung
M P
MP
Stevenson
D A
DA
Kung
H F
HF
D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging*; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D003543:Cysteamine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000493:pharmacokinetics; D005029:Ethylenediamines / Q000737:chemistry / Q000493:pharmacokinetics; D007202:Indicators and Reagents; D008024:Ligands; D008297:Male; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000737:chemistry / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D013667:Technetium / Q000737:chemistry / Q000493:pharmacokinetics
D005029:Ethylenediamines; D007202:Indicators and Reagents; D008024:Ligands; D019275:Radiopharmaceuticals; D003543:Cysteamine; D013667:Technetium